Expression analysis of microRNAs and mRNAs in myofibroblast differentiation of lung resident mesenchymal stem cells

Cong Wang; Honghui Cao; Shen Gu; Chaowen Shi; Xiang Chen; Xiaodong Han

doi:10.1016/j.diff.2019.11.002

Expression analysis of microRNAs and mRNAs in myofibroblast differentiation of lung resident mesenchymal stem cells

Differentiation. 2020 Mar-Apr:112:10-16. doi: 10.1016/j.diff.2019.11.002. Epub 2019 Dec 10.

Authors

Cong Wang¹, Honghui Cao², Shen Gu², Chaowen Shi², Xiang Chen², Xiaodong Han³

Affiliations

¹ Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of New Drug Discovery, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China.
² Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China.
³ Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address: [email protected].

PMID: 31838455
DOI: 10.1016/j.diff.2019.11.002

Abstract

Idiopathic pulmonary fibrosis (IPF) is a serious lung disease that involved the myofibroblast differentiation of lung resident mesenchymal stem cells (LR-MSCs). However, the specific molecular mechanisms of myofibroblast differentiation of LR-MSCs still remain a mystery. In this study, a comprehensive analysis of miRNAs and mRNAs changes in LR-MSCs treated with TGF-β1 was performed. Through computational approaches, the pivotal roles of differentially expressed miRNAs that were associated with tight junction, pathways in cancer, focal adhesion, and cytokine-cytokine receptor interaction were shown. Kruppel-like factor 4 (Klf4) and inhibitor of growth family, member 5 (Ing5) may be the targets for the therapy of pulmonary fibrosis by inhibiting myofibroblast differentiation of LR-MSCs and EMT. Collectively, a molecular paradigm for understanding myofibroblast differentiation of LR-MSCs in IPF was provided by the integrated miRNA/mRNA analyses.

Keywords: Idiopathic pulmonary fibrosis; Kruppel-like factor 4; Lung resident mesenchymal stem cells; Myofibroblast differentiation; miRNA/mRNA integrated analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / genetics
Gene Expression Regulation, Developmental / genetics
Humans
Idiopathic Pulmonary Fibrosis / genetics
Idiopathic Pulmonary Fibrosis / metabolism
Idiopathic Pulmonary Fibrosis / pathology
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors / genetics*
Lung / cytology
Lung / growth & development*
Lung / metabolism
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / metabolism
Mice
MicroRNAs / genetics*
Myofibroblasts / cytology
Myofibroblasts / metabolism
Transcription Factors / genetics*
Transforming Growth Factor beta1 / genetics
Transforming Growth Factor beta1 / metabolism*
Tumor Suppressor Proteins / genetics*

Substances

ING5 protein, human
KLF4 protein, human
Klf4 protein, mouse
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
MicroRNAs
Tgfb1 protein, mouse
Transcription Factors
Transforming Growth Factor beta1
Tumor Suppressor Proteins